-
Journal of Hematology & Oncology Feb 2021Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients.
METHODS
Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10/L) after 8 weeks of treatment.
RESULTS
The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment.
CONCLUSIONS
In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.
Topics: Adult; Double-Blind Method; Female; Humans; Hydrazones; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Pyrazolones; Receptors, Thrombopoietin; Treatment Outcome; Young Adult
PubMed: 33632264
DOI: 10.1186/s13045-021-01047-9 -
Molecules (Basel, Switzerland) Feb 2021The search for new biomedical applications of dendrimers has promoted the synthesis of new radical-based molecules. Specifically, obtaining radical dendrimers has opened... (Review)
Review
The search for new biomedical applications of dendrimers has promoted the synthesis of new radical-based molecules. Specifically, obtaining radical dendrimers has opened the door to their use in various fields such as magnetic resonance imaging, as anti-tumor or antioxidant agents, or the possibility of developing new types of devices based on the paramagnetic properties of organic radicals. Herein, we present a mini review of radical dendrimers based on polyphosphorhydrazone, a new type of macromolecule with which, thanks to their versatility, new metal-free contrast agents are being obtained, among other possible applications.
Topics: Dendrimers; Free Radicals; Humans; Hydrazones; Molecular Structure; Organophosphonates; Polymers
PubMed: 33669016
DOI: 10.3390/molecules26051230 -
Molecules (Basel, Switzerland) Oct 2022Many heterocyclic compounds can be synthetized using diaza-1,3-butadienes (DADs) as key structural precursors. Isolated and in situ diaza-1,3-butadienes, produced from... (Review)
Review
Many heterocyclic compounds can be synthetized using diaza-1,3-butadienes (DADs) as key structural precursors. Isolated and in situ diaza-1,3-butadienes, produced from their respective precursors (typically imines and hydrazones) under a variety of conditions, can both react with a wide range of substrates in many kinds of reactions. Most of these reactions discussed here include nucleophilic additions, Michael-type reactions, cycloadditions, Diels-Alder, inverse electron demand Diels-Alder, and aza-Diels-Alder reactions. This review focuses on the reports during the last 10 years employing 1,2-diaza-, 1,3-diaza-, 2,3-diaza-, and 1,4-diaza-1,3-butadienes as intermediates to synthesize heterocycles such as indole, pyrazole, 1,2,3-triazole, imidazoline, pyrimidinone, pyrazoline, -lactam, and imidazolidine, among others. Fused heterocycles, such as quinazoline, isoquinoline, and dihydroquinoxaline derivatives, are also included in the review.
Topics: Butadienes; Hydrazones; Imidazolidines; Imidazolines; Imines; Indoles; Isoquinolines; Lactams; Pyrazoles; Pyrimidinones; Quinazolines; Triazoles
PubMed: 36235245
DOI: 10.3390/molecules27196708 -
Chemical Reviews Aug 2017The formation of oximes and hydrazones is employed in numerous scientific fields as a simple and versatile conjugation strategy. This imine-forming reaction is applied... (Review)
Review
The formation of oximes and hydrazones is employed in numerous scientific fields as a simple and versatile conjugation strategy. This imine-forming reaction is applied in fields as diverse as polymer chemistry, biomaterials and hydrogels, dynamic combinatorial chemistry, organic synthesis, and chemical biology. Here we outline chemical developments in this field, with special focus on the past ∼10 years of developments. Recent strategies for installing reactive carbonyl groups and α-nucleophiles into biomolecules are described. The basic chemical properties of reactants and products in this reaction are then reviewed, with an eye to understanding the reaction's mechanism and how reactant structure controls rates and equilibria in the process. Recent work that has uncovered structural features and new mechanisms for speeding the reaction, sometimes by orders of magnitude, is discussed. We describe recent studies that have identified especially fast reacting aldehyde/ketone substrates and structural effects that lead to rapid-reacting α-nucleophiles as well. Among the most effective new strategies has been the development of substituents near the reactive aldehyde group that either transfer protons at the transition state or trap the initially formed tetrahedral intermediates. In addition, the recent development of efficient nucleophilic catalysts for the reaction is outlined, improving greatly upon aniline, the classical catalyst for imine formation. A number of uses of such second- and third-generation catalysts in bioconjugation and in cellular applications are highlighted. While formation of hydrazone and oxime has been traditionally regarded as being limited by slow rates, developments in the past 5 years have resulted in completely overturning this limitation; indeed, the reaction is now one of the fastest and most versatile reactions available for conjugations of biomolecules and biomaterials.
Topics: Biocompatible Materials; Catalysis; Hydrazones; Imines; Molecular Structure; Oximes
PubMed: 28640998
DOI: 10.1021/acs.chemrev.7b00090 -
Molecules (Basel, Switzerland) Apr 2023Photoresponsive biomaterials have garnered increasing attention recently due to their ability to dynamically regulate biological interactions and cellular behaviors in... (Review)
Review
Photoresponsive biomaterials have garnered increasing attention recently due to their ability to dynamically regulate biological interactions and cellular behaviors in response to light. This review provides an overview of recent advances in the design, synthesis, and applications of photoresponsive biomaterials, including photochromic molecules, photocleavable linkers, and photoreactive polymers. We highlight the various approaches used to control the photoresponsive behavior of these materials, including modulation of light intensity, wavelength, and duration. Additionally, we discuss the applications of photoresponsive biomaterials in various fields, including drug delivery, tissue engineering, biosensing, and optical storage. A selection of significant cutting-edge articles collected in recent years has been discussed based on the structural pattern and light-responsive performance, focusing mainly on the photoactivity of azobenzene, hydrazone, diarylethenes, and spiropyrans, and the design of smart materials as the most targeted and desirable application. Overall, this review highlights the potential of photoresponsive biomaterials to enable spatiotemporal control of biological processes and opens up exciting opportunities for developing advanced biomaterials with enhanced functionality.
Topics: Biocompatible Materials; Polymers; Drug Delivery Systems; Hydrazones; Light
PubMed: 37175122
DOI: 10.3390/molecules28093712 -
International Journal of Molecular... Aug 2021Hydrazide-hydrazones possess a wide spectrum of bioactivity, including antibacterial, antitubercular, antifungal, anticancer, anti-inflammatory, anticonvulsant,... (Review)
Review
Hydrazide-hydrazones possess a wide spectrum of bioactivity, including antibacterial, antitubercular, antifungal, anticancer, anti-inflammatory, anticonvulsant, antidepressant, antiviral, and antiprotozoal properties. This review is focused on the latest scientific reports regarding antibacterial, antimycobacterial, and antifungal activities of hydrazide-hydrazones published between 2017 and 2021. The molecules and their chemical structures presented in this article are the most active derivatives, with discussed activities having a hydrazide-hydrazone moiety as the main scaffold or as a side chain. Presented information constitute a concise summary, which may be used as a practical guide for further design of new molecules with antimicrobial activity.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Humans; Hydrazones
PubMed: 34502297
DOI: 10.3390/ijms22179389 -
Chemical Reviews Oct 2016Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds... (Review)
Review
Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C-N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.
Topics: Amidines; Aniline Compounds; Biological Products; Carbamates; Catalysis; Cyclization; Heterocyclic Compounds; Hydrazines; Hydrazones; Ligands; Palladium; Sulfonamides; Urea
PubMed: 27689804
DOI: 10.1021/acs.chemrev.6b00512 -
Biomedicine & Pharmacotherapy =... Jul 2023The hydrazones and hydrazide-hydrazones beside possessing crucial bioactivity can serve as useful intermediates in the synthesis of heterocyclic systems like... (Review)
Review
The hydrazones and hydrazide-hydrazones beside possessing crucial bioactivity can serve as useful intermediates in the synthesis of heterocyclic systems like 1,3-benzothiazin-4-one, 1,3-thiazolidin-4-one, azetidin-2-one and 1,3,4-oxadiazole derivatives. The azetidin-2-one derivatives show mainly antibacterial, antitubercular and antifungal activity as well as anti-inflammatory, antioxidant, anticonvulsant and antidepressant activity and activity against Parkinson's disease. This review is focused on the literature reports which consider the synthesis and biological properties of azetidin-2-one derivatives.
Topics: Hydrazones; Hydrazines; Anti-Bacterial Agents; Antifungal Agents; Anticonvulsants; Structure-Activity Relationship
PubMed: 37178574
DOI: 10.1016/j.biopha.2023.114853 -
The New England Journal of Medicine Feb 2017
Topics: Cardiotonic Agents; Humans; Hydrazones; Pyridazines; Sepsis
PubMed: 28229580
DOI: 10.1056/NEJMc1616632 -
The New England Journal of Medicine Feb 2017
Topics: Cardiotonic Agents; Humans; Hydrazones; Pyridazines; Sepsis
PubMed: 28225678
DOI: 10.1056/NEJMc1616632